Background: Currently, the cardiopulmonary machine with non-pulsatile pumps, which are low in internal circuit pressure and cause little damage to blood cells, is widely used. However, a great number of experimental studies shows that pulsatile perfusions are more useful than non-pulsatile counterparts in many areas, such as homodynamic, metabolism, organ functions, and micro-circulation. Yet, many concerns relating to pulsatile cardiopulmonary machines, such as high internal circuit pressure and blood cell damage, have long hindered the development of pulsatile cardiopulmonary machines. Against this backdrop, this study focuses on the safety and effectiveness of the pulsatile cardiopulmonary machines developed by a domestic research lab. Material and Method: The dual-pulsatile cardiopulmonary bypass experiment with total extracorporeal circulation was conducted on six calves, Extracorporeal circulation was provided between superior/inferior vena cava and aorta. The membrane oxygenator, which was placed between the left and right pumps, was used for blood oxygenation. Circulation took four hours. Arterial blood gas analysis and blood tests were also conducted. Plasma hemoglobin levels were calculated, while pulse pressure and internal circuit pressure were carefully observed. Measurement was taken five times; once before the operation of the cardiopulmonary bypass, and after its operation it was taken every hour for four hours. Result: Through the arterial blood gas analysis, PCO2 and pH remained within normal levels. PO2 in arterial blood showed enough oxygenation of over 100 mmHg. The level of plasma hemoglobin, which had total cardiopulmonary circulation, steadily increased to 15.87 $\pm$ 5.63 after four hours passed, but remained below 20 mg/㎗. There was no obvious abnormal findings in blood test. Systolic blood pressure which was at 97.5$\pm$5.7 mmHg during the pre-circulation contraction period, was maintained over 100 mmHg as time passed. Moreover, diastolic blood pressure was 72.2 $\pm$ 7.7 mmHg during the expansion period and well kept at the appropriate level with time passing by. Average blood pressure which was 83$\pm$9.2 mmHg before circulation, increased as time passed, while pump flow was maintained over 3.3 L/min. Blood pressure fluctuation during total extracorporeal circulation showed a similar level of arterial blood pressure of pre-circulation heart. Conclusion: In the experiment mentioned above, pulsatile cardiopulmonary machines using the doual-pulsatile structure provided effective pulsatile blood flow with little damage in blood cells, showing excellence in the aspects of hematology and hemodynamic. Therefore, it is expected that the pulsatile cardiopulmonary machine, if it becomes a standard cardiopulmonary machine in all heart operations, will provide stable blood flow to end-organs.
Background: We tested the effect of indomethacine and total spinal anesthesia on the improvement of placental flow during cardiopulmonary bypass on fetal lamb. Material and Method: Twenty fetuses at 120 to 150 days of gestation were subjected to bypass via trans-sternal approach with a 12 G pulmonary arterial cannula and 14 to 18 F venous cannula for 30 minutes. All ewes received general anesthesia with ketamine. In all the fetuses, no anesthetic agents were used except muscle relaxant. Ten served as a control group in which placenta was worked as an oxygenator during bypass (Control group). The remainder worked as an experimental group in which pretreatment with indomethacine and total spinal anesthesia was performed before bypass with the same extracorporeal circulation technique as control group (Experimental group). Observations were made every 10 minutes during a 30-minute bypass and 30-minute post bypass period. Result: Weights of the fetuses ranged from 2.2 to 5.2 kg. In Control group, means of arterial pressure decreased from 44.7 to 14.4 mmHg and means of Pa$CO_2$ increased from 61.9 to 129.6 mmHg at each time points during bypass. Flow rate was suboptimal (74.3 to 97.0 $m\ell$/kg/min) during bypass. All hearts fibrillated immediately after the discontinuation of bypass. On the contrary, in Experimental group, means of arterial pressure reamined higher (45.8 to 30 mmHg) during bypass (p<0.05). Means of Pa$CO_2$ were less ranging from 59.8 to 79.4 mmHg during bypass (P<0.05). Flow rates were higher (78.8 to 120.2 $m\ell$/kg/min) during bypass (p<0.05). There were slower deterioration of cardiac function after cessation of bypass. Conclusion: In this study, we demonstrated that the placental flow was increased during fetal cardiopulmonary bypass in the group pretreated with indomethacine and total spinal anesthesia. However, further studies with modifications of the bypass including a creation of more concise bypass circuit, and a use of axial pump are mandatory for the clinical application.
Purpose: N-13 ammonia uptake and retention in the myocardium is related to perfusion and metabolism. There are several potential advantages of N-13 ammonia positron emission tomography (PET) to detect myocardial ischemia, such as higher spatial resolution, greater counting efficiencies, and robust attenuation correction. But there are few reports comparing Tc-99m myocardial perfusion single photon emission tomography (MPS) and N-13 ammonia PET. We thus compared adenosine stress N-13 ammonia PET/CT and Tc-99m sestamibi MPS in patients with suspected coronary artery stenosis. Materials and Methods: Seventeen patients (male 13 : $63{\pm}11$ years old) underwent adenosine stress N-13 ammonia PET/CT (Discovery ST, GE), Tc-99m sestamibi MPS (dual head gamma camera, Hawkeye, GE) and coronary angiography within 1 week. N-13 ammonia PET/CT and Tc-99m sestamibi MPS images were assessed with a 20-segment model by visual interpretation and quantitative analysis using automatic quantitative software (Myovation, GE). Results: Both sensitivities and specificities of detecting an individual coronary artery stenosis were higher for N-13 ammonia PET/CT than Tc-99m sestamibi MPS (PET/CT: 91%/89% vs MPS: 65%/82%). N-13 ammonia PET/CT showed reversibility in 52% of segments that were considered non-reversibile by Tc-99m sestamibi MPS. In the 110 myocardial segments supplied by the stenotic coronary artery, N-13 ammonia PET/CT showed higher count densities than Tc-99m MPS on rest study (p < 0.01), and the difference of count density between the stress and the rest studies was also larger on N-13 ammonia PET/CT. Conclusion: Adenosine stress N-13 ammonia PET/CT had higher diagnostic sensitivity and specificity, more reversibility of perfusion defects and greater stress/rest uptake differences than Tc-99m sestamibi MPS. Accordingly, N-13 ammonia PET/CT might offer better assessment of myocardial ischemia and viability.
Park, Cheol;Hong, Su Hyun;Choi, Sung Hyun;Lee, Se-Ra;Leem, Sun-Hee;Choi, Yung Hyun
Journal of Life Science
/
v.25
no.12
/
pp.1384-1392
/
2015
Sagantang (SGT), a Korean multiherb formula comprising six medicinal herbs, Paeonia lactiflora Pall., Belamcanda chinensis (L.) DC, Gardenia jasminoides Ellis, Poria cocos Wolf, Cimicifuga heracleifolia Komarov, and Artractylodes japonica Koidzumi, was recorded in “Dongeuibogam.” The present study investigated the anticancer potential of SGT in AGS human gastric carcinoma cells. The results indicated that SGT treatment significantly inhibited the growth and viability of AGS cells in a dose-dependent manner, which was associated with the induction of apoptotic cell death, as evidenced by the formation of apoptotic bodies, in addition to chromatin condensation and DNA fragmentation, and the accumulation of annexin-V positive cells. The induction of apoptotic cell death by the SGT treatment was associated with up-regulation of Fas protein expression, truncation of Bid, and down-regulation of the anti-apoptotic Bcl-2 protein. The SGT treatment also effectively induced the loss of mitochondrial membrane potential, which was associated with the activation of caspases (caspase-3, -8, and -9) and degradation of poly (ADP-ribose) polymerase. However, a pan-caspase inhibitor significantly blocked the SGT-induced apoptosis and growth suppression in AGS cells. This study suggests that SGT induces caspase-dependent apoptosis through an extrinsic pathway by upregulating Fas, as well as through an intrinsic pathway by modulating Bcl-2 family members in AGS cells. The results suggest that SGT may be a potential chemotherapeutic agent for the control of human gastric cancer cells. However, further studies will be needed to confirm the potential of SGT in cancer prevention and therapy in an in vivo model and to identify biological active compounds of SGT.
Mutations in the APP gene lead to enhanced cleavage by ${\beta}-$ and ${\gamma}-secretase$, and increased $A{\beta}$ formation, which are closely associated with Alzheimer's disease (AD)-like neuropathological changes. Recent studies have shown that exercise training can ameliorate pathogenic phenotypes ($A{\beta}-42$, BDNF, GLUT-1 and HSP70) in experimental models of Alzheimer's disease. Here, we have used NSE/APPsw transgenic mice to investigate directly whether exercise training ameliorates pathogenic phenotypes within Alzheimer's brains. Sixteen weeks of exercise training resulted in a reduction of $A{\beta}-42$ peptides and also facilitated improvement of cognitive function. Furthermore, GLUT -1 and BDNF proteins produced by exercise training may protect brain neurons by inducing the concomitant expression of genes that encode proteins (HSP-70) which suppress stress induced neuron cell damages from APPsw transgenic mice. Thus, the improved cognitive function by exercise training may be mechanistically linked to a reduction of $A{\beta}-42$ peptides, possibly via activation of BDNF, GLUT-1, and HSP-70 proteins. On the basis of the evidences presented in this study, exercise training may represent a practical therapeutic management strategy for human subjects suffering from Alzheimer's disease.
A new photosensitizer, 9-Hydroxypheophorbide-a (9-HpbD-a), was derived from Spirulina platensis. We conducted a series of experiments, in vitro and in vivo, to evaluate the anticancer effect and mechanism of photodynamic therapy using 9-HpbD-a and 660 nm diode lasers on a squamous carcinoma cell line. We studied the cytotoxic effects of pheophytin-a, 9-HpbD-a, 9-HpbD-a red and 660 nm diode lasers in a human head and neck cancer cell line (SNU-1041). Cell growth inhibition was determined by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. The effects of 9-HpbD was higher than those of 9-HpbD-a red or pheophytin-a in PDT. We then tested the cytotoxic effects of 9-hydroxypheophorbide-a (9-HpbD-a) in vitro. The cultured SNU-I041 cells were treated with serial concentrations of 9-HpbD-a followed by various energy doses (0, 0.1, 0.5, 3.2 J/$cm^{2}$) and by various interval times (0, 3, 6, 9, 12 hr) until laser irradiation, then MTT assay was applied to measure the relative inhibitory effects of photodynamic therapy (PDT). Optimal laser irradiation time was 30 minutes and the cytotoxic effects according to incubation time after 9-HpbD-a treatment increased until 6 hours, after which it then showed no increase. To observe the cell death mechanism after PDT, SUN-I041 cells were stained by Hoechst 33342 and propidium iodide after PDT, and observed under transmission electron microscopy (TEM). The principal mechanism of PDT at a low dose of 9-HpbD-a was apoptosis, and at a high dose of 9-HpbD-a it was necrosis. PDT effects were also observed in a xenografted nude mouse model. Group I (no 9-HpbD-a, no laser irradiation) and Group II (9-HpbD-a injection only) showed no response (4/4, 100%), and Group III (laser irradiation only) showed recurrence (1/4,25%) or no response (3/4, 75 %). Group IV (9-HpbD-a + laser irradiation) showed complete response (10/16, 62.5%), recurrence (4/16, 25%) or no response (2/16, 12.5%). Group IV showed a significant remission rate compared to other groups (p<0.05). These results suggest that 9-HpbD-a is a promising photosensitizer for the future and that further studies on biodistribution, toxicity and mechanism of action would be needed to use 9-HpbD-a as a photosensitizer in the clinical setting.
This study is the first step for us toward improving high school students' capability of statistical inferences, such as obtaining and interpreting the confidence interval on the population mean that is currently learned in high school. We suggest 5 underlying concepts of 'discretion of contingency and inevitability', 'discretion of induction and deduction', 'likelihood principle', 'variability of a statistic' and 'statistical model', those are necessary to appreciate statistical inferences as a reliable arguing tools in spite of its occasional erroneous conclusions. We assume those 5 concepts above are to be gradually developing in their school periods and Korean mathematics textbooks of grades 1-12 were analyzed. Followings were found. For the right choice of solving methodology of the given problem, no elementary textbook but a few high school textbooks describe its difference between the contingent circumstance and the inevitable one. Formal definitions of population and sample are not introduced until high school grades, so that the developments of critical thoughts on the reliability of inductive reasoning could not be observed. On the contrary of it, strong emphasis lies on the calculation stuff of the sample data without any inference on the population prospective based upon the sample. Instead of the representative properties of a random sample, more emphasis lies on how to get a random sample. As a result of it, the fact that 'the random variability of the value of a statistic which is calculated from the sample ought to be inherited from the randomness of the sample' could neither be noticed nor be explained as well. No comparative descriptions on the statistical inferences against the mathematical(deductive) reasoning were found. Few explanations on the likelihood principle and its probabilistic applications in accordance with students' cognitive developmental growth were found. It was hard to find the explanation of a random variability of statistics and on the existence of its sampling distribution. It is worthwhile to explain it because, nevertheless obtaining the sampling distribution of a particular statistic, like a sample mean, is a very difficult job, mere noticing its existence may cause a drastic change of understanding in a statistical inference.
Objectives : This study was performed to determine whether an increase in abdominal obesity is an independent risk factor for impaired fasting glucose and type 2 DM. Methods : Among 24,212 adults over 30 years who undertook comprehensive medical screening examinations from Jan to Dec 1999, in a university hospital in Seoul, a total of 11,183 subjects were selected who had no DM at baseline and who were followed up more than once by Dec 2002. The average follow up period was 2.4 (${\pm}0.5$) years. DM was defined as having a fasting glucose level $\geq$ 126mg/dl, and impaired fasting glucose as showing a fasting glucose level between 110 and 125 mg/dl. Body weight, height and waist circumference (WC) were simultaneously measured with blood sampling. The relative risks (RRs) for DM and impaired fasting glucose by WC were calculated using Cox proportional hazard model. Ageadjusted rates were estimated by direct standardization using a reference population of 2000 from 30 to 80 years. Results : The average age of the subjects was 41.7 (${\pm}7.0$) years; males 41.2 (${\pm}6.5$) and females 45.6 (${\pm}9.2$). RRs for type 2 DM by WC with the reference group of WC < 80cm were as follows: 2.66 (95%, CI $0.55{\sim}12.8$) for WC of $80{\sim}89cm$ in men, 5.92 (95%, CI $1.08{\sim}32.3$) for WC $\geq$ 90 cm in men, and 2.64 (95%, CI $0.23{\sim}29.8$) for WC of $80{\sim}89cm$ in females. RRs for impaired fasting glucose by WC were 3.03 (95%, CI $2.18{\sim}4.22$) for WC $80{\sim}89cm$ in men, 6.10 (95%, CI $4.25{\sim}8.75$) for WC $\geq$ 90cm in men, and 1.56 (95%, CI $0.43{\sim}5.67$) for WC $80{\sim}89cm$ in women, and 8.08 (95%, CI $2.22{\sim}29.4$) for WC $\geq$ 90cm in females. These results remained significant after adjustment for age, BMI and fasting glucose concentrations at baseline in both sexes. Annual increment of more than 1 cm in WC was associated with the development of DM and impaired fasting glucose independently of age, sex, BMI, or presence of abdominal obesity. Conclusion : In Korean adults, abdominal obesity increased the risk for the development of type 2 diabetes and impaired fasting glucose. This result supports many other prospective studies suggesting abdominal obesity as a risk factor for type 2 diabetes.
Background: Most of the studies conducted have investigated the beneficial effects of ischemic preconditioning on normothermic myocardial ischemia. However, the effect of preconditioning could be attenuated through the use of multidose cold cardioplegia as practiced in contemporary clinical heart surgical procedures. The purpose of this study was to investigate whether preconditioning improves postischemic cardiac function in a model of $25^{\circ}C$ moderate hypothermic ischemic heart induced by cold cardioplegia in isolated rat hearts. Material and Method: The isolated Sprague-Dawley rat hearts were randomly assigned to four groups All hearts were perfused at 37$^{\circ}C$ for 20 minutes with Krebs-Henseleit solution before the baseline hemodynamic data were obtained, Group 1 consisted of preconditioned hearts that received 3 minutes of global ischemic preconditioning at 37$^{\circ}C$, followed by 5 minutes of reperfusion before 120 minutes of cardioplegic arrest (n=6). Cold (4$^{\circ}C$) St. Thomas Hospital cardioplegia solution was infused to induce cardioplegic arrest. Maintaining the heart at $25^{\circ}C$, infusion of the cardioplegia solution was repeated every 20 minutes throughout the 120 minutes of ischemic period. Group 2 consisted of control hearts that underwent no manipulations between the periods of equilibrium and 120 minutes of cardioplegic arrest (n=6). After 2 hours of cardioplegic arrest, Krebs solution was infused and hemodynamic data were obtained for 30 minuts (group 1, 2: cold cardioplegia group). Group 3 received two episodes of ischemic preconditioning before 30 min of 37$^{\circ}C$ normothermic ischemia and 30 minutes of reperfusion (n=6) Group 4 soloed as ischemic controls for group 3 (group 3, 4: warm ischemia group). Result: Preconditioning did not influence parameters such as left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), rate-pressure product (RPP) and left ventricular dp/dt (LV dp/dt) in the cold cardioplegia group. (p=NS) However, preconditioning before warm ischemia attenuated the ischemia induced cardiac dysfunction, Improving the LVSP, LVEDP, RPP, and LV dp/dt. Less leakage of CPK and LDH were observed in the ischemic preconditioning group compared to the control group (p<0.05). Conclusion: Ischemic preconditioning improved postischemic cardiac function after warm ischemia, but did not protect cold cardioplegic hearts.
Experimental induction of polycystic ovary (PCO) resembling some aspects of human PCO syndrome was produced using the long-acting compound estradiol valerate (EV). Our previous study on the role of Korean red ginseng total saponins (GTS) in a steroid-induced PCO rat model demonstrated that electro-acupuncture modulates nerve growth factor (NGF) concentration in the ovaries. In fact, the involvement of a neurogenic component in the pathology of PCO-related ovarian dysfunction is preceded by an increase in sympathetic outflow to the ovaries. In the present study, we tested the hypothesis that therapeutic GTS administration modulates sympathetic nerve activity in rats with PCO. This was done by analyzing NGF protein and NGF mRNA expression involved in the pathophysiological process underlying steroid-induced PCO. EV injection resulted in significantly higher ovarian NGF mRNA expression in PCO rats compared to control rats, and PCO ovaries were counteracted by GTS administration with significantly lower expression of NGF mRNA compared to EV treated ovaries. However, NGF protein was unaffected in both EV and GTS treated ovaries compared to control rats. These results indicate that EV modulates the neurotrophic state of the ovaries, which may be a component of the pathological process by which EV induces cyst formation and anovulation in rodents.
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